22 artificial homologues of farnesyl pyrophosphate were examined for the reactivity as substrate for squalene synthetase of pig liver microsomes. 16 of the homologues were found to be reactive to give corresponding squalene-like products. Extention of the omega-terminal of the carbon chain of farnesyl pyrophosphate is acceptable to the enzyme at least by two carbon atoms in either trans or cis direction (2E,6E)-3,7,11-Trimethyldodeca-2,6-dienyl- and (2E,6E)-3,7-dimethyldodeca-2,6-dienyl pyrophosphates are both good substrates, whereas (2E,6E)-3,7-dimethylundeca-2,6-dienyl-, (2E,6E)-3,7-dimethyl-trideca-2,6-dienyl-, (2E,6E)-3,7-dimethyltetradeca-2,6-dienyl-, (2E,6E)-3,7,10-trimethylundeca-2,6-dienyl-, and (2E,6E)-3,7,12-trimethyltrideca-2,6-dienyl pyrophosphates are poor substrates. These results indicate that the carbon chain length rather than 10,11-double bond is important for the reactivity as substrate. Replacement of 3-methyl of farnesyl pyrophosphate by an ethyl group or introduction of a methyl group at C-4 results in a complete loss of activity.